Oncological impact of perioperative blood transfusion in bladder cancer patients undergoing radical cystectomy: Do we need to consider storage time of blood units, donor age, or gender matching?

BACKGROUND: The oncological impact of perioperative blood transfusions (PBTs) of patients undergoing radical cystectomy (RC) because of bladder cancer (BCa) has been a controversial topic discussed in recent years. The main cause for the contradictory findings of existing studies might be the missing consideration of the storage time of red blood cell units (BUs), donor age, and gender matching. STUDY DESIGN AND METHODS: We retrospectively analyzed BCa patients who underwent RC in our department between 2004 and 2021. We excluded patients receiving BUs before RC, >10 BUs, or RC in a palliative setting. We assessed the effect of blood donor characteristics and storage time on overall survival (OS) and cancer-specific survival (CSS) through univariate and multivariable Cox regression analysis. We also performed a propensity score matching with patients who received BUs and patients who did not on a 1:1 ratio. RESULTS: We screened 1692 patients and included 676 patients for the propensity score matching. In the multivariable analysis, PBT was independently associated with worse OS and CSS (p < .001). Postoperative transfusions were associated with better OS (p = .004) and CSS (p = .008) compared to intraoperative or mixed transfusions. However, there was no influence of blood donor age, storage time, or gender matching on prognosis. DISCUSSION: In our study of BCa patients undergoing RC, we demonstrate that PBT, especially if administered intraoperatively, is an independent risk factor for a worse prognosis. However, storage time, donor age, or gender matching did not negatively affect oncological outcomes. Therefore, the specific selection of blood products does not promise any benefits.

A Systematic Review of New Imaging Technologies for Robotic Prostatectomy: From Molecular Imaging to Augmented Reality.

New imaging technologies play a pivotal role in the current management of patients with prostate cancer. Robotic assisted radical prostatectomy (RARP) is a standard of care for localized disease and through the already imaging-based console subject of research towards combinations of imaging technologies and RARP as well as their impact on surgical outcomes. Therefore, we aimed to provide a comprehensive analysis of the currently available literature for new imaging technologies for RARP. On 24 January 2023, we performed a systematic review of the current literature on Pubmed, Scopus and Web of Science according to the PRISMA guidelines and Oxford levels of evidence. A total of 46 studies were identified of which 19 studies focus on imaging of the primary tumor, 12 studies on the intraoperative tumor detection of lymph nodes and 15 studies on the training of surgeons. While the feasibility of combined approaches using new imaging technologies including MRI, PSMA-PET CT or intraoperatively applied radioactive and fluorescent dyes has been demonstrated, the prospective confirmation of improvements in surgical outcomes is currently ongoing.

Adverse Pathology after Radical Prostatectomy of Patients Eligible for Active Surveillance-A Summary 7 Years after Introducing mpMRI-Guided Biopsy in a Real-World Setting.

OBJECTIVE: Over the last decade, active surveillance (AS) of low-risk prostate cancer has been increasing. The mpMRI fusion-guided biopsy of the prostate (FBx) is considered to be the gold standard in preoperative risk stratification. However, the role of FBx remains unclear in terms of risk stratification of low-risk prostate cancer outside high-volume centers. The aim of this study was to evaluate adverse pathology after radical prostatectomy (RP) in a real-world setting, focusing on patients diagnosed with Gleason score (GS) 6 prostate cancer (PCa) and eligible for AS by FBx. SUBJECTS AND METHODS: Between March 2015 and March 2022, 1297 patients underwent FBx at the Department of Urology, Ludwig-Maximilians-University of Munich, Germany. MpMRI for FBx was performed by 111 different radiology centers. FBx was performed by 14 urologists from our department with different levels of experience. In total, 997/1297 (77%) patients were diagnosed with prostate cancer; 492/997 (49%) of these patients decided to undergo RP in our clinic and were retrospectively included. Univariate and multivariable logistic regression analyses were performed to evaluate clinical and histopathological parameters associated with adverse pathology comparing FBx and RP specimens. To compare FBx and systematic randomized biopsies performed in our clinic before introducing FBx (SBx, n = 2309), we performed a propensity score matching on a 1:1 ratio, adjusting for age, number of positive biopsy cores, and initial PSA (iPSA). RESULTS: A total of 492 patients undergoing FBx or SBx was matched. In total, 55% of patients diagnosed with GS 6 by FBx were upgraded to clinically significant PCa (defined as GS ≥ 7a) after RP, compared to 52% of patients diagnosed by SBx (p = 0.76). A time delay between FBx and RP was identified as the only correlate associated with upgrading. A total of 5.9% of all FBx patients and 6.1% of all SBx patients would have been eligible for AS (p > 0.99) but decided to undergo RP. The positive predictive value of AS eligibility (diagnosis of low-risk PCa after biopsy and after RP) was 17% for FBx and 6.7% for SBx (p = 0.39). CONCLUSIONS: In this study, we show, in a real-world setting, that introducing FBx did not lead to significant change in ratio of adverse pathology for low-risk PCa patients after RP compared to SBx.

An unusual case of struma ovarii.

SUMMARY: Struma ovarii is a teratoma of the ovaries predominantly composed of thyroid tissue. Hyperthyroidism associated with struma ovarii is rare, occurring in approximately 8% of cases. Due to the rarity of struma ovarii, available data are limited to case reports and small case series.We report on a 61-year-old female patient with known Hashimoto's thyroiditis on levothyroxine replacement therapy for years with transition to clinical and biochemical hyperthyroidism despite antithyroid medication with carbimazole (10 mg/day), new diagnosis of urothelial carcinoma and an adnexal mass suspicious of ovarian cancer. The patient underwent resection of the adnexal mass and histopathology revealed a mature teratoma predominantly composed of thyroid tissue showing high levels of sodium iodide symporter protein expression. Following struma ovarii resection and disappearance of autonomous production of thyroid hormones, the patient developed hypothyroidism with severely decreased thyroid hormone levels fT4 and fT3 (fT4 0.4 ng/dL, reference interval 0.9-1.7 and fT3 < 1.0 pg/mL, reference interval 2.0-4.4). This has previously been masked by continued thyroid-stimulating hormone suppression due to long-term hyperthyroidism pre-surgery indicating secondary hypothyroidism, in addition to primary hypothyroidism based on the known co-existing chronic lymphocytic thyroiditis of the orthotopic thyroid gland. Levothyroxine administration was started immediately restoring euthyroidism.This case illustrates possible diagnostic pitfalls in a patient with two concurrent causes of abnormal thyroid function. LEARNING POINTS: Struma ovarii is an ovarian tumor containing either entirely or predominantly thyroid tissue and accounts for approximately 5% of all ovarian teratomas. In rare cases, both benign and malignant struma ovarii can secrete thyroid hormones, causing clinical and biochemical features of hyperthyroidism. Biochemical features of patients with struma ovarii and hyperthyroidism are similar to those of patients with primary hyperthyroidism. In such cases, thyroid scintigraphy should reveal low or absent radioiodine uptake in the thyroid gland, but the presence of radioiodine uptake in the pelvis in a whole body radioiodine scintigraphy. We give advice on possible diagnostic pitfalls in a case with two simultaneous causes of abnormal thyroid function due to the co-existence of struma ovarii.

Dosimetry for (177)Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer.

PURPOSE: Dosimetry is critical to achieve the optimal therapeutic effect of radioligand therapy (RLT) with limited side effects. Our aim was to perform image-based absorbed dose calculation for the new PSMA ligand (177)Lu-DKFZ-PSMA-617 in support of its use for the treatment of metastatic prostate cancer. METHODS: Whole-body planar images and SPECT/CT images of the abdomen were acquired in five patients (mean age 68 years) for during two treatment cycles at approximately 1, 24, 48 and 72 h after administration of 3.6 GBq (range 3.4 to 3.9 GBq) (177)Lu-DKFZ-PSMA-617. Quantitative 3D SPECT OSEM reconstruction was performed with corrections for photon scatter, photon attenuation and detector blurring. A camera-specific calibration factor derived from phantom measurements was used for quantitation. Absorbed doses were calculated for various organs from the images using a combination of linear approximation, exponential fit, and target-specific S values, in accordance with the MIRD scheme. Absorbed doses to bone marrow were estimated from planar and SPECT images and with consideration of the blood sampling method according to the EANM guidelines. RESULTS: The average (± SD) absorbed doses per cycle were 2.2 ± 0.6 Gy for the kidneys (0.6 Gy/GBq), 5.1 ± 1.8 Gy for the salivary glands (1.4 Gy/GBq), 0.4 ± 0.2 Gy for the liver (0.1 Gy/GBq), 0.4 ± 0.1 Gy for the spleen (0.1 Gy/GBq), and 44 ± 19 mGy for the bone marrow (0.012 Gy/GBq). The organ absorbed doses did not differ significantly between cycles. The critical absorbed dose reported for the kidneys (23 Gy) was not reached in any patient. At 24 h there was increased uptake in the colon with 50 - 70 % overlap to the kidneys on planar images. Absorbed doses for tumour lesions ranged between 1.2 and 47.5 Gy (13.1 Gy/GBq) per cycle. CONCLUSION: The salivary glands and kidneys showed high, but not critical, absorbed doses after RLT with (177)Lu-DKFZ-PSMA-617. We suggest that (177)Lu-DKFZ-PSMA-617 is suitable for radiotherapy, offering tumour-to-kidney ratios comparable to those with RLT agents currently available for the treatment of neuroendocrine tumours. Our dosimetry results suggest that (177)Lu-DKFZ-PSMA-617 treatment with higher activities and more cycles is possible without the risk of damaging the kidneys.

The PolyScope: a modular design, semidisposable flexible ureterorenoscope system.

PURPOSE: To characterize the mechanical and optical properties of the PolyScope endoscope system and to examine the clinical outcome in patients who were undergoing ureteronephroscopy. MATERIALS AND METHODS: Mechanical assessment involved measurement of the deflection angle and irrigation flow rate. Optical resolution and distortion, field and angle of view, and light transmission and output formed the optical assessment. Clinical assessment was made in a series of consecutive ureteronephroscopy procedures. The optical cord was disconnected after each procedure, and the image fiber was assessed for damage. RESULTS: The mean value for the angle of maximum active tip deflection with an empty working channel was 265 degrees (261-275 degrees). Deflection was impaired most with insertion of the 3.0 F basket (10% decrease) and least with an indwelling 220 microm laser fiber (2% decrease). Irrigation flow rate was 57 mL/min with an empty working channel. Flow was reduced by 50% and 68%, with the insertion of a 200 microm or 365 microm laser probe, respectively, and by 92.5% with a 3.2F basket. No damage to the image fiber occurred. The PolyScope optics system could identify a target of about 0.125 mm at a distance of 2 to 4 mm, based on 3 line-pairs/mm needed for clear identification. Lithotripsy of renal calculi was performed for 40 stone burdens in 32 patients; the resulting stone-free rate was 87.5%. CONCLUSION: The novel semidisposable ureteroscope system PolyScope was simple to use, effective, and reliable in this preliminary clinical evaluation. It overcomes the inherent fragility of comparable devices, which renders the need for maintenance unnecessary.

Insights from a whole cystectomy specimen--association of primary small cell carcinoma of the bladder with transitional cell carcinoma in situ.

Small cell carcinoma of the urinary bladder is a rare entity known as an aggressive tumor. As it is rarely associated with transitional cell carcinoma in situ but more commonly with invasive transitional cell carcinoma, its origin is not well understood. We report a case of small cell carcinoma with coexisting transitional cell carcinoma in situ, where histologic mapping and parallel immunohistochemical and molecular analyses (TP53 mutation analyses, loss of heterozygosity) were performed. Immunohistochemical characterization (synaptophysin, thyroid transcription factor-1, chromogranin A, neuron specific enolase, CD56, CK, CK7, CK20, CD44v6, and p53) emphasized the morphology. Identical point mutations of TP53 were identified in invasive small cell carcinoma and transitional cell carcinoma in situ. No loss of heterozygosity of microsatellite markers D3S3050, D9S303, D9S304, D9S171, D9S775, D9S1748, D9S1751, D17S786, D17S918, and TP53alu was found in either component. We provide, for the first time, molecular evidence for the development of invasive small cell carcinoma out of transitional cell carcinoma in situ.